Metformin treatment lowers asymmetric dimethylarginine concentrations in patients with type 2 diabetes

This study was initiated to see if plasma asymmetric dimethylarginine (ADMA) concentrations decreased in hyperglycemic patients with type 2 diabetes following metformin treatment, either as monotherapy or following its addition to sulfonylurea-treated patients. Fasting plasma glucose, dimethylarginine, and L-arginine concentrations were measured before and 3 months after the administration of a maximally effective dose of metformin to 31 patients with type 2 diabetes in poor glycemic control (fasting plasma concentrations > 9.7 mmol/L), while being treated with either diet (n = 16) or a maximal amount of a sulfonylurea compound (n = 15). Fasting plasma glucose concentration (mean ± SEM) decreased to a similar degree (P < .01) in patients treated with either metformin alone (12.4 ± 0.5 to 9.5 ± 0.5 mmol/L) or when it was added to a sulfonylurea compound (14.1 ± 0.5 to 10.6 ± 0.9 mmol/L). The improvement in glycemic control was associated with similar decreases (P < .01) in ADMA concentrations in metformin (1.65 ± 0.21 to 1.18 ± 0.13 μmol/L) and sulfonylurea + metformin-treated patients (1.75 ± 0.13 to 1.19 ± 0.08 μmol/L). Plasma L-arginine concentrations were similar in the 2 groups at baseline and did not change in response to metformin. Thus, metformin treatment was associated with a favorable increase in the plasma L-arginine/ADMA ratio. These results provide the first evidence that plasma ADMA concentrations decrease in association with improved glycemic control in patients with type 2 diabetes and demonstrate that the magnitude of the change in metformin-treated patients was similar, irrespective of whether it was used as monotherapy or in combination with sulfonylurea treatment.